EZH2、MMP-2及MMP-9在肝癌侵袭转移中的作用及关系

The role and relationship of EZH2, MMP-2 and MMP-9 in HCC invasion and metastasis

目的检测果蝇zeste基因增强子的人类同源物2(EZH2)、基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)在原发性肝癌组织中的表达,分析三者表达的相关性,并明确三者表达与肝癌临床病理参数间的关系;探讨EZH2在肝癌细胞侵袭迁移中的作用以及对MMP-2和MMP-9表达的影响。方法qRT-PCR检测EZH2、MMP-2和MMP-9在肝癌组织中的表达;肝癌组织中三者表达的相关性采用Pearson相关分析;采用小干扰RNA转染构建EZH2表达下调的SMMC-7721肝癌细胞系;Transwell小室观察EZH2对SMMC-7721细胞侵袭、迁移的影响;qRT-PCR检测肝癌细胞中EZH2对MMP-2和MMP-9表达的影响。结果原发性肝癌组织中EZH2、MMP-2和MMP-9呈高表达,且其高表达与不良的临床病理因素相关;在肝癌组织中EZH2与MMP-9表达呈正相关;干扰EZH2表达抑制肝癌细胞侵袭、迁移和MMP-9表达。结论EZH2、MMP-2和MMP-9与肝癌的发生发展密切相关,可成为肝癌的潜在生物标记物和治疗靶点。

Objective To detect the expressions of enhancers of zeste homolog 2(EZH2), matrix metalloproteinase-2(MMP-2) and matrix metalloproteinase-9(MMP-9) in hepatocellular carcinoma(HCC) tissues, analyze the correlation of EZH2, MMP-2 and MMP-9 expressions in HCC tissues with the clinicopathological factors of HCC to explore the role of EZH2 in the invasion and migration of HCC cells and the regulatory effects of EZH2 on MMP-2 and MMP-9. Methods The expressions of EZH2, MMP-2 and MMP-9 in HCC tissues was detected by qRT-PCR. We analyzed the relationship of EZH2, MMP-2 and MMP-9 with the clinicopathological factors of HCC. Pearson correlation was used to analyze the correlation between EZH2, MMP-2 and MMP-9 expressions in HCC tissues. SMMC-7721 HCC cell lines with down-regulated EZH2 expression were constructed by small interfering RNA transfection. Transwell assay was used to observe the effects of EZH2 on invasion and migration of SMMC-7721 cells. qRT-PCR was used to detect the regulatory effects of EZH2 on MMP-2 and MMP-9 in HCC cells. Results EZH2, MMP-2 and MMP-9 expressions were increased in HCC tissues, and they were correlated with adverse clinicopathological factors. There was a significant correlation between the expressions of EZH2 and MMP-9 in HCC tissues. Deletion of EZH2 significantly inhibited the invasion and migration of HCC cells and inhibited MMP-9 expression in HCC cells. Conclusion EZH2, MMP-2 and MMP-9 are all closely associated with HCC progression, and they can be potential biomarkers and therapeutic targets for HCC.